Although the discipline of chemotherapy has produced a multitude of biologically active materials in the past several years, the emergence of certain lactones as structural entities which impart biological activities has been particularly noteworthy. We propose to study the biosynthesis of several molecules which exhibit both lactone structural features and anti-tumor properties. By employing radioactive tracers and crude kinetic studies to follow "turnover" of metabolites we plan to identify biosynthetic intermediates in the pathways leading to gaillardin (a sesquiterpene lactone possessing anti-tumor properties) and pentalenolactone (a potent antibiotic and potential anti-tumor agent which is suspected to be a novel sesquiterpene from a Streptomyces species). We intend to elucidate the biosynthetic pathways to alpha-methylenelactones, provide experimental support for the biogenetic proposals on sesquiterpene biosynthesis, and demonstrate normal terpenoid biosynthesis in a new class of organisms. Not only do we expect to utilize these techniques to isolate and identify additional potential anti-tumor agents (as biosynthetic intermediates), but we also plan to investigate a method of organic synthesis for producing potentially biologically active alpha-methylenebutyrolactones from the common isopropenyl group of isoprenoids. This synthetic procedure involves ring closure of an allylic alcohol and oxygenation of the resulting cyclic ether.